Comparison of the effectiveness and safety of insulin and oral hypoglycemic drugs in the treatment of gestational diabetes mellitus: a meta-analysis of 26 randomized controlled trials

Abstract

Objective

Oral hypoglycemic drugs for the treatment of gestational diabetes mellitus (GDM) are still controversial because they can pass through the placenta. The purpose of this meta-analysis is to evaluate the safety and effectiveness of oral hypoglycemic drugs.

Methods

PubMed, Ovid Embase, Web of Science, and Cochrane databases were systematically searched (inception to 20 April 2021). Rev Man 5.0 was used to analyze the data. A random-effects model was used to compute the summary risk estimates.

Results

There were 26 randomized controlled trials (RCTs) involving 4921 GDM patients which were included in this meta-analysis. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.06 to 2.45; I²=40%; p < .05), hypertension (OR, 1.42; 95% CI, 1.02 to 1.99; I²=0%; p < .05), hypoglycemia (OR, 3.93; 95% CI, 1.27 to 12.19; I²=0%; p < .05), neonatal hypoglycemia (OR, 1.92; 95% CI, 1.34 to 2.76; I²=41%; p < .0001), neonatal jaundice (OR, 2.70; 95% CI, 1.12 to 6.52; I²=0%; p < .05), and Neonatal Intensive Care Unit Admission (OR, 1.46; 95% CI, 1.09 to 1.95; I²=39%; p < .05), but the risk of neonatal macrosomia (OR, 1.67; 95% CI, 1.12 to 2.40; I²=0%; p < .05) and neonatal injury (OR, 0.70; 95% CI, 0.55 to 0.89; I²=0%; p < .01) is lower.

Conclusions

Metformin is comparable with insulin in glycemic control and neonatal outcomes and has the potential to replace insulin therapy in clinical practice. Glyburide is behind metformin and insulin, and more RCTs are needed to verify its safety.

胰岛素和口服降糖药治疗妊娠期糖尿病的有效性和安全性比较：26项随机对照试验的荟萃分析 摘要

目的：口服降糖药治疗妊娠期糖尿病（GDM）仍有争议, 因为它们可以通过胎盘。本荟萃分析的目的是评估口服降糖药物的安全性和有效性。

方法：系统检索起始日期至2021年4月20日PubMed、Ovid Embase、Web of Science和Cochrane数据库。Rev Man 5.0用于分析数据。使用随机效应模型来计算风险估计汇总。

结果：共有26项随机对照试验（RCT）, 涉及4921名GDM患者纳入本荟萃分析。与二甲双胍相比, 胰岛素显著增加了先兆子痫（优势比[OR], 1.61；95%可信区间[CI], 1.06至2.45；I2=40%；p<0.05）、高血压（OR, 1.42；95%CI, 1.02至1.99；I2=0%；p<0.05）、低血糖（OR, 3.93；95%CI, 1.27至12.19；I2=0%；p<0.05）的风险, 新生儿低血糖（OR, 1.92；95%CI, 1.34至2.76；I2=41%；p<0.0001）；新生儿黄疸（OR, 2.70；95%CI, 1.12至6.52；I2=0%；p<0.05）；新生儿重症监护病房入院（OR, 1.46；95%CI, 1.09至1.95；I2=39%；p<0.05）, 但新生儿巨大儿（OR, 1.67；95%CI, 1.12至2.40；I2=0%；p<0.05）和新生儿损伤（OR, 0.70；95%CI, 0.55至0.89；I2=0%；p<0.01）的风险较低。

结论：二甲双胍在血糖控制和新生儿预后方面与胰岛素相当, 在临床实践中有可能取代胰岛素治疗。格列本脲落后于二甲双胍和胰岛素, 需要更多的随机对照试验来验证其安全性。

Keywords:

• Gestational diabetes mellitus
• insulin
• oral antidiabetic drugs
• meta-analysis

Acknowledgements

The authors thank all authors of included studies in this meta-analysis, and we’re especially grateful for the authors who provided us with the original data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

CL, CG, and XJ conceived the initial research project. CL and CG conduct a literature search, quality evaluation, and data extraction, and XJ provided important opinions. CL and CG performed the statistical analysis and explained the data together with XJ. CL wrote the first draft of the manuscript. All authors critically revised the manuscript and approved the final version.

Data availability statement

Available data and materials are included in this manuscript.

Additional information

Funding

This work was supported by The National Nature Science Foundation of China [Grant No. 31870135].